Autism : a genetic anomaly could be a therapeutic target

Health 6 December, 2017


Published the 05.12.2017 at 18h12


Keywords :

autismeneuronecircuits neuronauxgèneUbe3A

In children with autism, the exaggerated expressions of a gene linked to autism spectrum disorders (ASD), and the overproduction of the protein it encodes, could lead to a deficit of connections between nerve cells during the brain’s development.
The copy number variation of the Ube3A gene and over-production of the protein E6AP (” overexpression “) that result are known as being directly related to autism spectrum disorders (ASD), however, the cellular defects and molecular accurate to the origin of the disorder was less well understood.

Too strong expression of the Ube3A gene

Heng-Ye Man, and his colleagues show that overexpression in neurons of the Ube3A gene leads to increased production of protein E6AP which it is bound, which leads to a reduction in the number and length of connections (” dendritic branching ” between brain cells.
The modification of the dendritic arborization induced by the excess of E6AP is a retraction of dendrites by thinning and fragmentation of the tip of their branches, resulting in the shortening or elimination of these dendrites, ” as for a tree that would have been too pruned and whose branches no longer reach the nearby trees “.

Decrease of the connectivity between nerve cells

The connectivity of the neurons in the brain is reduced, which disrupts the establishment of neural circuits that we must develop in the course of the learning and maturation of the brain.
These fundamental data are from a new study conducted on cultures of human neurons and a mouse model with autism spectrum disorders, published in the journal, The Journal of Neuroscience.
They show that the same pathway is responsible for these changes in cortical neurons and hippocampal in rats and in mice overexpressing Ube3A. These results suggest that an activity E6AP high leads to a reduction in excessive dendrites, compared to normal.

Better understanding of disorders

The growth and refinement of the divisions of dendrites, branches on nerve cells that form tree like structures, allow you to increase connections with other neurons in the brain.
This “branching tree” of nerve cells is a crucial factor in the development of the brain during the first years of life, which helps to optimize the function of neural circuits.
Changes in the number and structure of the dendrites have been observed in patients with autism spectrum disorders, which are usually diagnosed during this same period of development.

Determination of a therapeutic target

These results reveal the important role of the hyperfunction of the couple Ube3A gene – protein E6AP in the alteration in the development of the connectivity of nerve cells in the brain in autism spectrum disorders.

The absence of dendritic arborization and synapse formation between nerve cells related to the overexpression of this gene and the hypersecretion of protein that is linked to it, provide new insights into the pathogenesis of autism spectrum disorders Ube3A / E6AP-dependent. As well as a possible new therapeutic target.